Naicons Srl., Viale Ortles 22/4, 20139 Milano, Italy.
Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
J Nat Prod. 2021 Feb 26;84(2):204-219. doi: 10.1021/acs.jnatprod.0c00807. Epub 2021 Jan 26.
Despite an excellent track record, microbial drug discovery suffers from high rates of rediscovery. Better workflows for the rapid investigation of complex extracts are needed to increase throughput and to allow early prioritization of samples. In addition, systematic characterization of poorly explored strains is seldomly performed. Here, we report a metabolomic study of 72 isolates belonging to the rare actinomycete genus , using a workflow of commonly used open access tools to investigate its secondary metabolites. The results reveal a correlation of chemical diversity and strain phylogeny, with classes of metabolites exclusive to certain phylogroups. We were able to identify previously reported metabolites, including the ureylene-containing oligopeptide antipain, the thiopeptide siomycin including new congeners, and the ribosomally synthesized peptides sphaericin and lantibiotic 97518. In addition, we found that strains can produce the siderophore desferrioxamine or a salinichelin-like peptide. Analysis of the genomes of three newly sequenced strains led to the detection of 59 gene cluster families, of which three were connected to products found by LC-MS/MS profiling. This study demonstrates the value of metabolomic studies to investigate poorly explored taxa and provides a first picture of the biosynthetic capabilities of the genus .
尽管微生物药物发现有着出色的记录，但仍存在高比例的重复发现现象。为了提高通量并允许对样品进行早期优先排序，需要更好的快速研究复杂提取物的工作流程。此外，对探索较少的菌株进行系统表征的情况很少。在这里，我们报告了对 72 株属于稀有放线菌属的菌株进行的代谢组学研究，使用了一组常用的开放获取工具来研究其次生代谢产物。结果表明，化学多样性与菌株系统发育之间存在相关性，某些分类群特有的代谢物类别。我们能够鉴定出以前报道过的代谢物，包括含有脲基的寡肽抑蛋白酶、含有新同系物的噻肽硅霉素以及核糖体合成的肽球孢菌素和兰尼丁素 97518。此外，我们发现某些菌株可以产生铁载体去铁胺或盐霉素样肽。对三个新测序菌株基因组的分析导致检测到 59 个基因簇家族，其中三个与 LC-MS/MS 分析中发现的产物有关。这项研究表明代谢组学研究在探索探索较少的分类群方面具有价值，并提供了该属生物合成能力的初步图景。
